Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases
Autor(a) principal: | |
---|---|
Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/microorganisms10071331 http://hdl.handle.net/11449/241251 |
Resumo: | Several neurotropic viruses are members of the flavivirus and alphavirus families. Infections caused by these viruses may cause long-term neurological sequelae in humans. The continuous emergence of infections caused by viruses around the world, such as the chikungunya virus (CHIKV) (Alphavirus genus), the zika virus (ZIKV) and the yellow fever virus (YFV) (both of the Flavivirus genus), warrants the development of new strategies to combat them. Our study demonstrates the inhibitory potential of the water-soluble vitamin riboflavin against NS2B/NS3pro of ZIKV and YFV and nsP2pro of CHIKV. Riboflavin presents a competitive inhibition mode with IC50 values in the medium µM range of 79.4 ± 5.0 µM for ZIKV NS2B/NS3pro and 45.7 ± 2.9 µM for YFV NS2B/NS3pro. Against CHIKV nsP2pro, the vitamin showed a very strong effect (93 ± 5.7 nM). The determined dissociation constants (KD) are significantly below the threshold value of 30 µM. The ligand binding increases the thermal stability between 4 °C and 8 °C. Unexpectedly, riboflavin showed inhibiting activity against another viral protein; the molecule was also able to inhibit the viral entry of CHIKV. Molecular dynamics simulations indicated great stability of riboflavin in the protease active site, which validates the repurposing of riboflavin as a promising molecule in drug development against the viruses presented here. |
id |
UNSP_b945ace9ae2d76ff45b2a4cd04af11d8 |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/241251 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteasesalphaviruscompetitive inhibitorflavivirusNS2B/NS3pronsP2proriboflavinSeveral neurotropic viruses are members of the flavivirus and alphavirus families. Infections caused by these viruses may cause long-term neurological sequelae in humans. The continuous emergence of infections caused by viruses around the world, such as the chikungunya virus (CHIKV) (Alphavirus genus), the zika virus (ZIKV) and the yellow fever virus (YFV) (both of the Flavivirus genus), warrants the development of new strategies to combat them. Our study demonstrates the inhibitory potential of the water-soluble vitamin riboflavin against NS2B/NS3pro of ZIKV and YFV and nsP2pro of CHIKV. Riboflavin presents a competitive inhibition mode with IC50 values in the medium µM range of 79.4 ± 5.0 µM for ZIKV NS2B/NS3pro and 45.7 ± 2.9 µM for YFV NS2B/NS3pro. Against CHIKV nsP2pro, the vitamin showed a very strong effect (93 ± 5.7 nM). The determined dissociation constants (KD) are significantly below the threshold value of 30 µM. The ligand binding increases the thermal stability between 4 °C and 8 °C. Unexpectedly, riboflavin showed inhibiting activity against another viral protein; the molecule was also able to inhibit the viral entry of CHIKV. Molecular dynamics simulations indicated great stability of riboflavin in the protease active site, which validates the repurposing of riboflavin as a promising molecule in drug development against the viruses presented here.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Deutsche ForschungsgemeinschaftInstitute of Biological Information Processing (IBI-7 Structural Biochemistry) Forschungszentrum Jülich GmbHInstitut für Physikalische Biologie Heinrich-Heine-Universität Düsseldorf UniversitätsstraßeCenter of Integrated Sciences Campus Cimba Federal University of Tocantins, TOInstitute of Physics Federal University of Mato Grosso do Sul, MSInstituto Superior de Educação Ceres FACERES Medical School, SPLaboratório de Pesquisas em Virologia Departamento de Doenças Dermatológicas Infecciosas e Parasitárias Faculdade de Medicina de São José do Rio Preto-FAMERP, SPDepartment of Pathology University of Texas Medical BranchMultiuser Center for Biomolecular Innovation Department of Physics IBILCE São Paulo State University, SPJuStruct: Jülich Centre for Structural Biology Forchungszentrum JülichMultiuser Center for Biomolecular Innovation Department of Physics IBILCE São Paulo State University, SPFAPESP: 2020/08615-8Deutsche Forschungsgemeinschaft: 267205415Deutsche Forschungsgemeinschaft: SFB 1208Forschungszentrum Jülich GmbHUniversitätsstraßeFederal University of TocantinsFederal University of Mato Grosso do SulFACERES Medical SchoolFaculdade de Medicina de São José do Rio Preto-FAMERPUniversity of Texas Medical BranchUniversidade Estadual Paulista (UNESP)Forchungszentrum JülichEberle, Raphael J.Olivier, Danilo S.Amaral, Marcos S.Pacca, Carolina C.Nogueira, Mauricio L.Arni, Raghuvir K. [UNESP]Willbold, DieterCoronado, Monika A.2023-03-01T20:53:37Z2023-03-01T20:53:37Z2022-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/microorganisms10071331Microorganisms, v. 10, n. 7, 2022.2076-2607http://hdl.handle.net/11449/24125110.3390/microorganisms100713312-s2.0-85133142521Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMicroorganismsinfo:eu-repo/semantics/openAccess2023-03-01T20:53:37Zoai:repositorio.unesp.br:11449/241251Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-06T00:02:28.054554Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases |
title |
Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases |
spellingShingle |
Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases Eberle, Raphael J. alphavirus competitive inhibitor flavivirus NS2B/NS3pro nsP2pro riboflavin |
title_short |
Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases |
title_full |
Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases |
title_fullStr |
Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases |
title_full_unstemmed |
Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases |
title_sort |
Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases |
author |
Eberle, Raphael J. |
author_facet |
Eberle, Raphael J. Olivier, Danilo S. Amaral, Marcos S. Pacca, Carolina C. Nogueira, Mauricio L. Arni, Raghuvir K. [UNESP] Willbold, Dieter Coronado, Monika A. |
author_role |
author |
author2 |
Olivier, Danilo S. Amaral, Marcos S. Pacca, Carolina C. Nogueira, Mauricio L. Arni, Raghuvir K. [UNESP] Willbold, Dieter Coronado, Monika A. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Forschungszentrum Jülich GmbH Universitätsstraße Federal University of Tocantins Federal University of Mato Grosso do Sul FACERES Medical School Faculdade de Medicina de São José do Rio Preto-FAMERP University of Texas Medical Branch Universidade Estadual Paulista (UNESP) Forchungszentrum Jülich |
dc.contributor.author.fl_str_mv |
Eberle, Raphael J. Olivier, Danilo S. Amaral, Marcos S. Pacca, Carolina C. Nogueira, Mauricio L. Arni, Raghuvir K. [UNESP] Willbold, Dieter Coronado, Monika A. |
dc.subject.por.fl_str_mv |
alphavirus competitive inhibitor flavivirus NS2B/NS3pro nsP2pro riboflavin |
topic |
alphavirus competitive inhibitor flavivirus NS2B/NS3pro nsP2pro riboflavin |
description |
Several neurotropic viruses are members of the flavivirus and alphavirus families. Infections caused by these viruses may cause long-term neurological sequelae in humans. The continuous emergence of infections caused by viruses around the world, such as the chikungunya virus (CHIKV) (Alphavirus genus), the zika virus (ZIKV) and the yellow fever virus (YFV) (both of the Flavivirus genus), warrants the development of new strategies to combat them. Our study demonstrates the inhibitory potential of the water-soluble vitamin riboflavin against NS2B/NS3pro of ZIKV and YFV and nsP2pro of CHIKV. Riboflavin presents a competitive inhibition mode with IC50 values in the medium µM range of 79.4 ± 5.0 µM for ZIKV NS2B/NS3pro and 45.7 ± 2.9 µM for YFV NS2B/NS3pro. Against CHIKV nsP2pro, the vitamin showed a very strong effect (93 ± 5.7 nM). The determined dissociation constants (KD) are significantly below the threshold value of 30 µM. The ligand binding increases the thermal stability between 4 °C and 8 °C. Unexpectedly, riboflavin showed inhibiting activity against another viral protein; the molecule was also able to inhibit the viral entry of CHIKV. Molecular dynamics simulations indicated great stability of riboflavin in the protease active site, which validates the repurposing of riboflavin as a promising molecule in drug development against the viruses presented here. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-07-01 2023-03-01T20:53:37Z 2023-03-01T20:53:37Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3390/microorganisms10071331 Microorganisms, v. 10, n. 7, 2022. 2076-2607 http://hdl.handle.net/11449/241251 10.3390/microorganisms10071331 2-s2.0-85133142521 |
url |
http://dx.doi.org/10.3390/microorganisms10071331 http://hdl.handle.net/11449/241251 |
identifier_str_mv |
Microorganisms, v. 10, n. 7, 2022. 2076-2607 10.3390/microorganisms10071331 2-s2.0-85133142521 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Microorganisms |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129576000290816 |